Adverse Effects of Blood Transfusion

Manifestations of Acute HTR

1. Antibody binds to red cells (patient antibody and donor cells) 2. Activation of complement 3. Activation of mononuclear phagocytes and cytokines 4. Activation of coagulation DIC (disseminatedintravascular coagulation) 5. Shock and renal failure

What is the (approximate) incidence of bacterial contamination in a unit of Apheresis PLATELETS?

1/1000 ~ 1/4000

A temperature rise of 1°C or more occurring in association with transfusion, with no abnormal results in the transfusion reaction investigation, usually indicates which of the following reactions? A) febrile B) circulatory overload C) hemolytic D) anaphylactic

A) febrile Febrile non-hemolytic transfusion reactions are defined as fever of 1°C or greater (over baseline temperature) during or after transfusion, with no other reason for the elevation then transfusion. There is also no evidence of hemolysis in the transfusion reaction investigation. [AABB Tech Manual 2017, 581; Harmening 2012, 375]

What blood group incompatibility is most commonly associated with acute hemolytic transfusion reactions?

ABO

Antibodies linked to Intravascular Hemolysis

ABO Antibodies: Anti-A Anti-B Others: ---anti-H produced in people with the Bombay blood group (see the H blood group) ---anti-Jka (see the Kidd blood group), ---anti-P, P1, Pk (see the P blood group system). (https://www.ncbi.nlm.nih.gov/books/NBK2265/)

TRALI happens when Donor anti-HLA antibodies activate in the plasma and:

Activate recipient neutrophils that will migrate and enter and fill the lungs

The primary reason behind Acute HTR is:

Activation of complement

What two plasma ions are bound by citrate?

Calcium and magnesium

Congestive heart failure, severe headache and/or peripheral edema occuring soon after transfusion is indicative of which type of transfusion reaction? A) hemolytic B) febrile C) anaphylactic D) circulatory overload

D) circulatory overload Transfusion-induced hypERvolemia causing edema and congestive heart failure is a feature of transfusion associated circulatory overload (TACO). HypERvolemia is NOT a complication of a hemolytic, febrile, or anaphylactic transfusion reaction. [AABB Tech Manual 2017, p 584]

Patients at greatest risk of developing TACO may include: A) Children B) Elderly people C) Patients with chronic normovolemic anemia D) Patients with Sickle Cell Disease E) All of the above

E

In transfusion medicine, what does the acronym TACO stand for?

Transfusion-associated circulatory overload

What type of medication is commonly used to treat a hypotensive reaction?

Vasopressors

What are the typical Symtpoms of Acute HTR?

• Fever [Temp Increase of More Than 1C) • chills/rigors • nausea and vomiting • Hypotension (low blood pressure) •hemoglobinemia •hemoglobinuria

Lab Testing for Extravascular Hemolysis

• Positive DAT • Positive antibody screen following an elution • Positive Antibody Screen • Consumption of RBCs in spleen - ↓ Hgb/Hct

What are the expected clinical findings with an acute hemolytic transfusion reaction?

(1) Fever, back pain, hypotension (2) disseminated intravascular coagulation, oliguria (renal failure)

In an Acute HTR what are characteristics of Extravascular hemolysis?

(1) an atypical antibody reacts with a foreign antigen donor RBCs. ----- Splenic macrophage phagocytosis destruction of donor RBCs coded by the atypical antibody (2) jaundice commonly occurs. ----- Unconjugated bilirubin (UCB) is the end product of macrophage degradation of hemoglobin. (3) type II hypersensitivity reaction

What are the expected laboratory findings with an acute hemolytic transfusion reaction?

(1) positive direct Coombs test -----IgG antibody or C3b is coating donor of RBCs (2) positive indirect Coombs test ----atypical antibody present in serum (3) NO increase in Hgb over pretransfusion levels (4) hemoglobinuria ----- sign of intravascular hemolysis (5) Jaundice -----sign of Extravascular hemolysis

What are the expected clinical findings with allergic transfusion reaction?

(1)Urticaria with pruritus (2) fever, tachycardia, wheezing (3) potential for anaphylactic shock (4) mild cases are treated with antihistamines

List the various types of adverse reactions to Transfusion:

-Acute Hemolytic Transfusion Reaction - Delayed Hemolytic Transfusion Reaction -Febrile NonHemolytic Transfusion Reaction (FNHTR) -Allergic Transfusion Reactions -Anaphylactic Transfusion Reactions -Transfusion-Related Acute Lung Injury (TRALI) -Transfusion-Associated Circulatory Overload (TACO) -Transfusion Associated Dyspnea -Hypotensive Transfusion Reactions -Transfusion-Associated Graft versus Host Disease (TA-GVHD)

Antibodies linked to EXTRAvascular Hemolysis:

...Instead, their presence (specifically, the Fc component of the antibody) is recognized by IgG-Fc receptors of macrophages, which aids the phagocytosis of the cells. ---Antibodies directed at antigens of the Rh blood group mediate this type of RBC removal. ---Other types of antibody that bind to the donor RBCs may bind the complement component C3b without activating the entire cascade. This further aids the phagocytosis by macrophages that have C3b receptors. Such antibodies include those directed against antigens of the ABO, Duffy, and Kidd blood groups.

What is the incidence of IgA deficiency?

1:700

Which listed transfusion reaction is most associated with transfused patients lacking IgA immunoglobulin? A) Anaphylactic B) Hemolytic C) Febrile D) TACO E) Allergic

A

Which test should be performed when a patient has a reaction to transfused plasma products? A) immunoglobulin levels B) T cell count C) hemoglobin levels D) red cell enzymes

A) immunoglobulin levels A reaction to plasma products may be found in IGA deficient person who has formed anti-IGA antibodies. Immunoglobulin levels would aid in this determination. Selective IGA deficiency is the most common immunodeficiency disease and is characterized by serum IGA levels below 5 mg/dL. IGA is usually absent from secretions, but the B cell count is usually normal

Name that Transfusion Reaction! Pathogenesis -type II hypersensitivity reaction. -Intravascular hemolysis (ABO blood group incompatibility IgM antibodies) (Recipient antibodies directed against donor red blood cell (RBC) antigens activate complement, leading to destruction of RBCs in the blood vessels) or -Extravascular hemolysis (host antibody reaction against foreign antigen on donor RBCs) Clinical Presentation -fever -hypotension -tachypnea -tachycardia -flank pain -hemoglobinemia (intravascular) -hemoglobinuria -jaundice (extravascular hemolysis)

Acute hemolytic transfusion reaction (HTR)

What is the most common antibody implicated in post-transfusion purpura (PTP)?

Anti-HPA-1a

A transfusion reaction that usually appears rapidly during the transfusion termed "warm" and that may result in fever, shock, or death is which of the following? A) Hemolytic B) Bacterial Contamination C) TACO D) Allergic E) FNHTR

B

Which listed transfusion reaction may result from an anamnestic response following a secondary exposure to donor RBCs? A) IHTR B) Alloimmunization C) Anaphylactoid reaction D) TACO E) TA-GVHD

B

What is the increase in the risk percentage for developing antibodies against red cell antigens (RBC alloimmunization) for patients who are characterized as chronically transfused patients? A) 1% - 4% B) 2% - 8% C) 5% - 10% D) 20% - 50%

B) 2% - 8% In chronically transfused patients, the risk for them developing antibodies against red cell antigens (RBC alloimmunization) increases by 2% - 8%.

Which of the following is a characteristic of ABO hemolytic disease of the newborn (HDN) rather than Rh HDN due to anti-D? A) Age-adjusted normocytic anemia B) Newborn may develop anemia and jaundice in the first pregnancy C) Positive direct Coombs' on umbilical cord RBCs D) Severe anemia requiring an exchange transfusion E) Unconjugated hyperbilirubinemia

B) Newborn may develop anemia and jaundice in the first pregnancy In ABO HDN, O mothers already have anti-A and B IgG natural antibodies that react with different antigens in blood group A and B RBCs. Because IgG crosses the placenta, if the fetus is blood group A or B, the antibody will attach to the RBC and be removed by fetal splenic macrophages leading to a mild extravascular hemolytic anemia. In Rh HDN due to anti-D, the mother must first be sensitized by an Rh positive fetus before antibodies can cross the placenta and hemolyze fetal Rh positive cells in future pregnancies.

The use of only male donors as a source of plasma for transfusion is a method to reduce the risk of: A) allergic B) TRALI C) hemolytic D) TACO (circulatory overload)

B) TRALI TRALI is most commonly caused by donor HLA or granulocyte-specific antibodies (human neutrophil antibodies HNA) that react with recipeint antigens, causing damage to the lung basement membrane and bilateral pulmonary edema within 6 hours of transfusion. Multiparous females are more likely to have antibodies than males. Using male donors as the sole source of plasma products is a strategy for reducing the risk of TRALI. [AABB Tech Manual 2017, p582-584; Harmening 2012, p376-377]

Hives and itching are symptoms of which the following transfusion reaction? A) febrile B) allergic C) circulatory overload D) bacterial

B) allergic Allergic reactions are a type I immediate hypersensitivity reaction to an allergen and plasma. Most are mild reactions shown by urticaria (hives, swollen red wheals) which may cause itching. [AABB Tech Manual 2017, p581]

In ABO hemolytic transfusion reactions, complement is activated via which of the following pathways? A) alternative B) classical C) lectin D) polyclonal

B) classical ABO antibodies are very efficient at activating complement via the classical pathway. ABO antibodies can be potent hemolysins and cause intravascular destruction of incompatible red cells. [Harmening 2012, p61, 370]

A patient had a hemolytic reaction to blood transfused eight days ago. What is most likely cause? A) immediate, non-immunologic probably due to volume overload B) delayed immunologic, probably due to an antibody such as anti-Jka C) delayed nonimmunologic, probably due to iron overload D) immediate, immunologic, probably due to a clerical error, ABO incompatibility

B) delayed immunologic, probably due to an antibody such as anti-Jka A transfusion reaction that occurs several days after transfusion of blood products is probably a delayed immunologic reaction due to an antibody formed against owner images. This is a classic example of a reaction caused by an antibody such as anti-Jka.

What would be the result of group A blood given to an O patient? A) non-immune transfusion reaction B) immediate hemolytic transfusion reaction C) delayed hemolytic transfusion reaction D) febrile non-hemolytic transfusion reaction

B) immediate hemolytic transfusion reaction Group A blood given to a group O patient would cause an immediate hemolytic transfusion reaction because a group O patient has anti-A and anti-B antibodies and would destroy A cells.

What is the usual finding when a chest x-ray is performed on a patient experiencing a transfusion-related acute lung injury (TRALI) ?

Bilateral infiltrates

Transfused plasma constituents resulting in immediate erythema, itching, and hives best typify which of the following transfusion reactions? A) HTR B) DHTR C) Allergic D) Iron OVerload E) Alloimmunization

C

Which of the following antibodies is most responsible for IHTR? A) Anti-Le^a B) Anti-N C) Anti-A D) Anti-M E) Anti-D

C

Antibodies to which of the following blood components is the most frequent cause of febrile nonhemolytic transfusion reactions? A) Platelets B) Packed red blood cells C) Granulocytes D) Plasma

C) Granulocytes The most common type of febrile nonhemolytic transfusion reaction (FNHTR) occurs as the result of cytotoxic antibodies or leukoagglutinins (leukocyte antibodies) formed against the white blood cells present in the donor unit. Granulocyte concentrates are collected white blood cells used in the treatment of patients diagnosed with severe neutropenia. Due to this component type being comprised of primarily white blood cells, leukocyte depletion filters cannot be used. A standard blood administration filter may be used with this component. One approach to preventing a FNHTR is to perform a prestorage leukocyte reduction for whole blood, platelet, and packed red blood cell components. Plasma components do not contain enough white blood cells to warrant the use of a leukocyte reduction filter. Therefore, there is minimal risk for a FNHTR to occur.

Posttransfusion purpura is usually caused by: A) anti-A B) white cell antibodies C) anti-HPA-1a D) platelet wash-out

C) anti-HPA-1a Posttransfusion purpura (PTP) is caused by platelet-specific alloantibody in a previously immunized recipient. Transfused donor platelets in blood products are destroyed, with concomitant destruction of the recipient's own platelets, through unknown mechanisms. The usual antibody specificity is HPA-1a. [AABB Tech Manual 2017, p591-592; Harmening 2012, p382]

What may be found in the serum of a person who is exhibiting signs of TRALI (transfusing related acute lung injury) ? A) red blood cell alloantibody B) IgA antibody C) anti-leukocyte antibody D) allergen

C) anti-leukocyte antibody TRALI is associated with antibodies to human leukocyte antigens or neutrophil antigens, which react with patient granulocytes and cause acute respiratory insufficiency

Coughing, hypoxemia, and difficult breathing are symptoms of which of the following transfusion reactions? A) febrile B) allergic C) circulatory overload D) hemolytic

C) circulatory overload Transfusion-associated circulatory overload (TACO) is hypERvolemia manifested by coughing, cyanosis, and cardiogenic pulmonary edema. [AABB Tech Manual 2017, p584; Harmening 2012, p378]

A patient received five units of fresh frozen plasma (FFP) and developed a severe anaphylactic reaction. He has a history of respiratory and gastrointestinal infections. Post-transfusion studies showed all five units to be ABO-compatible. What immunologic test would help to determine the cause of this transfusion reaction? A) complement levels, particularly C3 and C4 B) flow cytometry for T-cell counts C) measurement of immunoglobulins D) NBT test for phagocytic function

C) measurement of immunoglobulins the patient had an anaphylactic reaction to a plasma product. This, combined with a history of respiratory and gastrointestinal infections, suggest a selective IGA deficiency. A low serum IGA and normal IgG substantiate the diagnosis of selective IGA deficiency. Such patients frequently produce anti-IGA, which is often responsible for severe transfusion reaction when ABO - compatible plasma is administered.

A 32-year-old woman who is five days postpartum develops fever, low back pain, and yellow describe coloration in her eyes. Immediately after delivery she had massive hemorrhage due to the retained placenta, for which she received three units of packed RBCs. Her pre-transfusion antibody screen was negative, and all units of blood were compatible. A similar obstetric mishap occurred during her first pregnancy 14 years ago, which required three units of packed RBCs to normalize her blood loss. Her current CBC demonstrates a 2 g/dL drop in hemoglobin concentration when compared to the post transfusion level prior to discharge from hospital. Both direct and indirect Coombs is test results are positive. A pink discoloration is noted in the serum. The total bilirubin is 3.5 mg/dL with predominately unconjugated bilirubin present on fractionation. The serum alanine aminotransferase ALT concentration is 20 U/L. If Which of the following best describes the mechanism for jaundice? A) donor IgG antibodies destroying patient RBCs B) patient anti-HLA antibodies are destroying patient leukocytes C) patient IgG antibodies are destroying transfused donor RBCs D) post transfusion fever due to cytomegalovirus E) post transfusion hepatitis due to hepatitis C

C) patient IgG antibodies are destroying transfused donor RBCs The patient had a delayed transfusion reaction. She is a positive direct and indirect Coombs' test, free Hb in her serum, and a significant drop in her post transfusion Hb concentration after leaving the hospital. It is likely that she was sensitized during her first pregnancy, but the antibody titers were too low to detect and handle the screen she had prior to transfusion during her recent hospitalization.

A patient has symptoms indicating a possible hemolytic transfusion reaction. What should be done immediately? A) stop the transfusion and discard the unit B) contact the patient's doctor to ask if the transfusion should be stopped C) stop the transfusion and call the patient's doctor to report the reaction D) have patient blood samples sent to the lab to investigate the reaction

C) stop the transfusion and call the patient's doctor to report the reaction AABB Standards state that any sign of a possible transfusion reaction requires the transfusion be stopped, and the patient's doctor contacted immediately. [AABB/TS Standards 2018, p 90]

In the United States, what government agency needs to be notified if a death is associated with a transfusion?

Centre for Biologics Evaluation and Research (CBER) of the Food and Drug Administration (FDA)

What are three standard tests initially performed on a post-transfusion specimen when a transfusion reaction is suspected?

Check for visible hemolysis, ABO group, and direct anti-globulin test (DAT). Clerical checks are also performed at the bedside and in the laboratory

All of the following are part of the preliminary evaluation of a transfusion reaction, EXCEPT: A) check pre- and post-transfusion samples for color of serum B) perform ABO and Rh recheck C) DAT on the post-transfusion sample D) Panel on pre- and post-transfusion samples

D) Panel on pre- and post-transfusion samples The preliminary evaluation of a transfusion reaction includes checking the color of serum, and performing ABO and Rh checks and a DAT on the post-transfusion sample. A panel would not be part of the preliminary workup

Symptoms of dyspnea, hypoxemia, and pulmonary edema within 6 hours of transfusion is most likely which type of reaction? A) anaphylactic B) hemolytic C) febrile D) TRALI

D) TRALI Noncardiogenic pulmonary edema, dyspnea, hypotension, and hypoxemia occurring within 6 hours of transfusion are clinical symptoms of TRALI. [AABB Tech Manual 2017, p582]

Transfusion of which blood product is most likely to cause circulatory overload in patients? A) Platelets B) Fresh frozen plasma C) Red blood cells D) Whole blood

D) Whole blood Many patients only require a specific therapy from blood products, such as an increase in oxygen-carrying capability or coagulation factors. To give these patients whole blood would cause a large increase in blood volume, potentially leading to transfusion-associated circulatory overload. Platelets contain very little plasma or volume. Transfusion of platelets does not create a circulatory overload. Fresh frozen plasma can cause circulatory overload if the recipient receives a high volume or high rate of infusion or if the patient has an underlying condition affecting the heart or lungs. However, fresh frozen plasma does not contain as great of a volume as whole blood and is generally safer to use as long as it is properly transfused. Red blood cells can cause transfusion-associated circulatory overload. However, since the majority of plasma has been removed from these units, the likelihood of transfusion-associated circulatory overload is typically low unless the patient receives a large volume or high rate of infusion or if the patient has an underlying condition that affects the heart or lungs.

Congestive heart failure, severe headache and/or peripheral edema occurring soon after transfusion is indicative of which type a transfusion reaction? A) hemolytic B) febrile C) anaphylactic D) circulatory overload

D) circulatory overload Transfusion induced hypERvolemia causing edema and congestive heart failure is a feature of transfusion-associated circulatory overload (TACO). Hypervolemia is not a complication of a hemolytic, febrile, or anaphylactic transfusion reaction. [AABB Tech Manual 2017, p584]

After receiving incompatible blood, a patient develops a transfusion reaction in the form of back pain, fever, shortness of breath, and hematuria. Which one of the following statements best classifies this type of immunologic reaction? A) systemic anaphylactic reaction B) systemic immune complex reaction C) delayed -type hypersensitivity reaction D) complement-mediated cytotoxicity reaction E) T-cell-mediated cytotoxicity reaction

D) complement-mediated cytotoxicity reaction A blood transfusion reaction is a type II hypersensitivity reaction that is mediated by antibodies reacting against antigens present on the surface of blood group antigens or irregular antigens present on the donors red blood cells. Type II hypersensitivity reactions result from attachment of antibodies to changed cell surface antigens or to normal cell surface antigens. Complement-mediated cytotoxicity occurs when IgM or IgG binds to a cell surface antigen with complement activation and consequent cell membrane damage or lysis. Blood transfusion reactions and autoimmune hemolytic anemia are examples of this form. Systemic anaphylaxis is a type I hypersensitivity reaction in which mast cells or basophils that are bound to IgE antibodies are re-exposed to an allergen, which leads to a release of vasoactive amines that cause edema and broncho- and vasoconstriction. Sudden death can occur. Systemic immune complex reactions are found in type III reactions and are due to circulating antibodies that form complexes upon re-exposure to an antigen (such as foreign serum) , which then activates complement. This process is followed by chemotaxis and aggregation of neutrophils, which leads to release of lysosomal enzymes and eventual necrosis of tissue and cells. Serum sickness and Arthus reactions are examples of type III reactions. Delay type hypersensitivity is type IV is due to previously desensitized T lymphocytes, which release length all kinds upon re-exposure to the antigen. This takes time-perhaps up to several days following exposure. The tuberculin reaction is the best known example. T cell mediated cytotoxicity lysis of cells by cytotoxic T cells in response to cancer last, allogenic tissue, and virus-cells. These cells have CD8 antigens on their surfaces. (Kumar, pp 197-204)

A patient has become refractory to platelet transfusion. Which of the following are probable causes? A) transfusion of Rh-incompatible platelets B) decreased pH of the platelets C) development of an alloantibody with anti-D specificity D) development of antibodies to HLA antigen

D) development of antibodies to HLA antigen Alloimmunization to HLA antigens can result in refractoriness to random donor platelet transfusions. [AABB Tech Manual 2017, p447; Harmening 2012, p487]

During blood transfusion, clotting of transfused blood is associated with: A) ABO incompatibility B) minor blood group incompatibility C) Rh incompatibility D) transfusion through Ringer's lactate E) transfusion through 5% dextrose and water

D) transfusion through Ringer's lactate Most transfusion reactions are hemolytic and are due to clerical errors that result in administration of blood with major (ABO) and minor antigen incompatibility. Interestingly, Rh incompatibility is not associated with intravascular hemolysis. Administration of blood through hypotonic solution such as 5% dextrose and water results in swelling of the erythrocytes and hemolysis. Calcium -containing solutions such as ringers lactate cause clotting within the intravenous line rather than hemolysis may lead to pulmonary embolism. Delay transfusion reactions, caused by a presumed anamnestic immune response that occurs 3-21 days after blood is infused, resulting hemolytic anemia (Schwartz, 7/e, pp 97-98)

What would you expect the DAT result to be on a person that had a Febrile TR?

DAT-Negative

What are two transfusion medicine laboratory tests that are commonly performed to confirm a delayed hemolytic transfusion reaction?

Direct antiglobulin test (DAT) and antibody screen/identification (against red blood cell antigens)

The result of the DAT after a delayed transfusion reaction may be: A) Positive B) Mixed-field C) Positive because of complement coating only D) Negative E) All of the above

E

An afebrile blood group O, Rh NEGative (O-) 75-year-old man has a massive lower gastrointestinal bleed from sigmoid diverticulosis. He has to be transfused with blood group O, Rh POSitive (O+) blood, because no group O, Rh NEGative (O-) blood is currently available in the blood banks in the area. He states that he is been transfused once in the past without any problems. In the pretransfusion workup, the patient has a negative antibody screen and a compatible major crossmatch for units of group O, Rh POSitive (O+) blood. Midway through an infusion of the third unit of blood he develops fever, headache, and tachycardia. The transfusion stopped and a transfusion workup in the blood bank exhibits the following unopposed transfusion specimen of patient blood: Patient temperature: 103°F (39.4°C) Patient blood pressure: 130/86 mmHg Patient pulse: 130 beats/minute Patient plasma: clear Patient antibody screen: Negative Patient direct Coombs': NEGative Patient urine: NEGative for dipstick blood Which of the following best explains the mechanism for the transfusion reaction? A) delayed hemolytic transfusion reaction B) error in the major crossmatch C) hemolytic transfusion reaction related to receiving Rh positive blood D) histamine-related transfusion reaction E) patient anti-HLA antibodies directed against donor leukocytes

E) patient anti-HLA antibodies directed against donor leukocytes The patient has a febrile transfusion reaction. In these reactions, the recipient has anti-human leukocyte antigen (HLA) antibodies directed against foreign HLA antigens on donor leukocytes. Destruction of the donor leukocytes releases pyrogens causing fever as well as other findings such as chills, headache, and flushing.

What things are associated with IgG mediated hemolysis?

Extravascular hemolysis Spherocytosis

The collecting facility is to report donor fatalities, and the compatibility testingfacility is to report recipient fatalities within 24 hours to the:

FDA

Name that Transfusion Reaction! Pathogenesis type II hypersensitivity reaction host antibodies against donor HLA antigens and leukocytes Clinical Presentation -fever( increase in body temperature of more than 1°C (with or without chills) -headaches -chills -flushing

Febrile non-hemolytic transfusion reaction (FNHTR)

What are the two defining symptoms of a febrile, nonhemolytic transfusion reaction (FNHTR)?

Fever and/or chills

What is one way to differentiate TRALI from TACO?

Fever commonly occurs in TRALI

Allergic Transfusion Reactions can range from:

From minor urticarial skin effects to anaphylactic shock and death. [Type I [Immediate] Hypersensitivity reaction due to IgE antibodies]

What is the Co-op between hospitals and the AABB and CDC for reporting all adverse events?

Hemovigilance program

Allergic transfusion reactions are mediated by what antibody (isotype)?

IgE

What two classes of antibodies are commonly associated with allergic transfusion reactions?

IgG or IgE

With the release of anaphylatoxins and cytokines, a patient may go into Renal Shock/Failure due to:

Inadequate blood flow to tissues (ischemia)

How can transfusion-associated graft versus host disease (TA-GvHD)be prevented?

Irradiate cellular products for patients who are at increased risk

Patients at risk of GVHD [Siblings, ICP's] will receive:

Irradiated blood units

What is the Etiology of TRALI?

Pathway 1: Donor leukocyte antibodies (usually anti-HLA or anti- neutrophil) react with recipient leukocyte antigens. 1) Antibody activates complement 2) C3a and C5a cause release of histamines and serotonin from basophils and platelets 3) Leads to: a) Formation of neutrophil emboli, which aggregate in the capillaries of the lungs, causing alveolar damage b) Release of chemicals that damage the pulmonary endothelium Pathway 2: Recipient has had a preexisting condition that activates their pulmonary endothelium allowing neutrophils to stick to the endothelium and primes the neutrophils. 1) When the recipient is transfused, antibodies or other chemicals(Biologic Response Modifiers or BRMs) in the donor unit activate the neutrophils. 2) Activated neutrophils release chemicals that damage the pulmonary endothelium. c. Damaged pulmonary endothelium allows fluid to leak into alveolar space, causing the symptoms seen in TRALI. Bilateral pulmonary infiltrates visible on chest X-ray. (Diagnostic finding!)

Name that Transfusion Reaction! Pathogenesis Anti-HPA-1a, a platelet antibody, destroys transfused platelets and patient's own platelets. Antibody coated platelets are cleared by the mononuclear phagocytic system. Clinical Presentation ---Transfusion recipient experiences a sudden drop in platelet count (platelet count <10,000) within 2 weeks post transfusion. -Bleeding from mucous membranes, GI and urinary tracts have been reported. ---May be fatal if there is an intracranial hemorrhage. ---Usually occurs in multiparous women or patients who have been previously transfused. --- Usually self-limited with recovery in 21 days. If necessary, treatment includes IVIG, steroids, or exchange plasmapheresis. ---Platelet transfusions are notrecommended. ---When absolutely necessary, additional platelet transfusions may be from HPA-1a negative donors, or units that yield a compatible platelet crossmatch.

Post-Transfusion Purpura (PTP)

Name that Transfusion Reaction! Pathogenesis Hypervolemia due to excessive volume or rapid infusion of blood components Clinical Presentation -Congestive heart failure (CHF) -Dyspnea, dry cough, cyanosis -Increase in systolic B.P., tachycardia -Elevated serum troponin -Increased brain natriuretic peptide (BNP). -----Post to pretransfusion ratio of 1.5 and a post transfusion BNP of 100pg/mL or greater -Severe headache

TACO (transfusion-associated circulatory overload)

Name that Transfusion Reaction! Pathogenesis most commonly caused by donor HLA or granulocyte-specific antibodies (human neutrophil antibodies HNA) that react with recipeint antigens, causing damage to the lung basement membrane and bilateral pulmonary edema within 6 hours of transfusion Clinical Presentation Symptoms occur within 6 hours of transfusion (usually within 1-2 hours) - Respiratory distress, cough, cyanosis -. Chills and fever -. Hypotension (May first present as hypertension then become hypotensive) - Bilateral pulmonary edema

Transfusion Related Acute Lung Injury (TRALI)-

Name that Transfusion Reaction! Pathogenesis Second leading cause of transfusion related death ----incomplete cleaning of donor venipuncture site ---Septicemia in donor ----Improper handling during preparation of components (such as port contamination when thawing or pooling) Organisms involved a. Gram positive skin contaminants 1) Coagulase negative Staphylococcus species 2) Staphylococcus aureus 3) Streptococcus species b. Gram negative species - most frequently due to undetected donor bacteremia. Reaction may be due to endotoxins released by these bacteria. Reactions due to Gram negative bacteria are usually more severe than those due to Gram positive. Species involved include: 1) Yersinia entercolitica- Grows well in cold temperatures, especially when iron enriched (as in RBCs) 2) Escherichia coli 3) Pseudomonas species 4) Klebsiella species 5) Serratia species Seen more frequently following platelet transfusions due to the favorable growth conditions created with platelet storage (room temperature).Refrigeration of RBCs retards bacterial growth, minimizing the number of septic reactions seen following transfusion of this component Clinical Presentation ---Symptoms develop rapidly, often within first 15 minutes of transfusion ---Rapid onset of high fever ------ Temperature > 38.5°C (or >101°F) or increase of >2°C (or > 3.5°F) from pretransfusion temperature -Chills and rigors -Hypotension -Dry, flushed skin -Shock -Abdominal cramps, vomiting, and diarrhea -DIC -Renal failure

Transfusion-Related Sepsis

True/False Antibodies stimulated by blood transfusion or pregnancy, such as Rh antibodies, are termed immune antibodies and are usually IgG, in contrast to naturally occurring antibodies , such as ABO antibodies, which are made in response to environmental antigens present in food and bacteria, and are usually IgM.

True

Typical Indications for IRRAdiated Blood Components

certain groups of immunocompromised patients at particular risk of TA-GvHD: ---pts with Hematologic malignancies ---transplant recipients ---patients with congenital or T-cell immunodeficiency, eg, Wiskott-Aldrich ---recipients of granulocyte concentrates ---patients receiving nucleoside analogs: (flucytosine, Ribavarin,tenofovir, abacavir,Fludarabine,etc) --- treatment with purine analogue drugs: -Allopurinol -Nelarabine a purine analog used for T-cell acute lymphoblastic leukemia -pentostatin(Hairy cell Leukemia), -cladribine (2-chlorodeoxyadenosine) -Thioguanine -Fludarabine -Mercaptopurine --- patients with Hodgkin lymphoma ---recipients of donations from related donors ----HSCT pts ---fetuses and neonates who have received an intrauterine transfusion. ---infants with prematurity, low birth weight, or HDFN (Source: Practical Clinical Pathology, 2nd Ed, Mais, p104)

After an IHTR, the recipient's serum bilirubin may return to normal in: A) 5hrs B) 12hrs C) 48hrs D) 3hrs E) 24hrs

e

What is the most commonly associated blood component known to cause TRALI?

high plasma volume blood components from parous female donors

Fill in the Blank TA-GVHD can be prevented by ________________ blood components before transfusion

irradiating

Lab testing for Intravascular Hemolysis:

• Positive DAT possible • Release of RBC contents in vessels ↑ plasma and urine hemoglobin • Haptoglobin binds to free hemoglobin ↓ serum haptoglobin • Disseminated intravascular coagulation (DIC) ↓ platelets, factors V, VIII, fibrinogen, PT, aPTT ↑ fibrin degradation products

What is an Acute Hemolytic Reaction?

•Onset immediately after exposure •Intravascular hemolysis - RBCs destroyed within circulation

What is a Delayed Hemolytic Reaction?

•Onset of signs and symptoms occurs within days to weeks after transfusion •Extravascular hemolysis - cleared through phagocytosis by macrophages ---Bone marrow, liver, and spleen

Transfusion Associated Circulatory Overload [TACO] overview:

∙ Occurs when a patient's cardiopulmonary system *exceeds volume capacity*. ∙ Typically happens with children ∙ At risk patients: heart conditions, chronic anemia, children ∙ Symptoms: ▫Coughing/wheezing ▫ shortness of breath/cyanosis ▫ tachycardia ▫ hypertension ▫ pulmonary edema ∙ Treatment: ▫ diuretics ∙ Prevention: transfuse slowly, small volumes

Individuals who have recieved massive transfusions can have some adverse side effects from the total blood volume replacement. List a few:

∙ Transfusion hemosiderosis: ◦ Excess iron in organs ◦ Transfuse with Iron Chelators ∙Coagulopathath: ◦ citrated blood locks up Ca++ ∙ Citrate toxicity: ◦ ↑ volumes of citrated blood ∙ Hypothermia: ◦Massive transfusion of cold products reduces core temperature ◦ Use blood warmers

Anaphylactic T.R.'s

∙ Usual cause: ▫ *IgE* antibodies in an IgA deficient recipient to IgA normally found in plasma ▫ Formed via Preg. & Transfusions ∙ Symptoms: ▫ Hypotension, Shock ▫ Can react to small amount of plasma in first unit transfused ▫ Occurs on 2nd transfusion after being sensitized through the 1st transfusion ∙ Treatment: ▫ epinephrine ∙ Prevention: ▫ transfuse only *washed RBCs* or transfuse blood products from IgA deficient donors

In an Acute HTR, complement will:

▫ *Opsonization* ▫ *Anaphylatoxin generation* ▫ *Cell lysis*

Non- Hemolytic T.R. types:

▫ Febrile ▫ Allergic ▫ TACO ▫ TRALI

Delayed [>24 hr] T.R. types:

▫ Hemolytic ▫ Infectious disease ▫ Graft vs. Host disease

Immune-Mediated T.R. types:[Abs reacting to Ags on RBCs, WBCs, PLTs (HLA), or plasma proteins]

▫ Hemolytic Transfusion Reaction ▫ TRALI ▫ Anaphylactic

Acute [<24 hr] T.R. types:

▫ Hemolytic reactions (<24 hrs) ▫ Allergic - (<2 hrs) ▫ ABO Incompatibility ▫ TRALI and TACO (<6 hrs)

Nonimmune-mediated T.R. types:

▫ Hemosiderosis (iron overload) ▫ Citrate toxicity ▫ Circulatory overload (TACO)

Once complement is activated, phagocytes from the spleen come int play and generate cytokines. Cytokines will induce what in the patient?

▫ Hypotension ▫ Fever ▫ Activation of B and T cells

Hemolytic T.R. types:

▫ Immune-mediated (antibody) ▫ Physical or chemical damage to RBCs (freezing)